(See also Overview of Decreased Erythropoiesis Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction... read more .)
The term aplastic anemia commonly implies a panhypoplasia of the bone marrow with cytopenias in at least two hematopoietic lineages. In contrast, pure red blood cell (RBC) aplasia Pure Red Blood Cell Aplasia Acquired pure red blood cell aplasia is a disorder of erythroid precursors that results in an isolated normocytic anemia. White blood cells and platelets are not affected. Symptoms result from... read more is restricted to the erythroid cell line.
Etiology of Aplastic Anemia
True aplastic anemia (most common in adolescents and young adults) is idiopathic in about half of cases. Recognized causes are
Chemicals (eg, benzene, inorganic arsenic)
Drugs (eg, antineoplastic drugs, antibiotics, nonsteroidal anti-inflammatory drugs, antiseizure drugs, acetazolamide, gold salts, penicillamine, quinacrine)
Hepatitis (seronegative for hepatitis viruses)
Pregnancy
Radiation
Viruses (Epstein-Barr virus and cytomegalovirus)
The precise mechanism remains unclear but in the majority of cases involves an immune attack on the hematopoietic stem cell. Clonal hematopoiesis is frequently present, and there is a risk of progression to a myeloid malignancy.
Symptoms and Signs of Aplastic Anemia
The onset of aplastic anemia usually is insidious, often occurring over weeks or months after exposure to a toxin, though occasionally it can be acute.
In aplastic anemia, anemia may cause weakness and easy fatigability while severe thrombocytopenia Symptoms and Signs Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more 
may cause petechiae, ecchymosis, and bleeding from the gums, into the conjunctivae, or other tissues. Agranulocytosis Neutropenia Neutropenia is a reduction in the blood neutrophil count. If it is severe, the risk and severity of bacterial and fungal infections increase. Focal symptoms of infection may be muted, but fever... read more commonly causes life-threatening infections. Splenomegaly is absent unless induced by transfusion hemosiderosis.
Diagnosis of Aplastic Anemia
Complete blood count (CBC) and reticulocyte count
Bone marrow examination
Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia. Severe aplastic anemia is defined by a bone marrow with < 30% cellularity (hypocellularity) and the presence of ≥ 2 of the following:
Absolute neutrophil count < 500/microL (< 0.5 × 109/L)
Absolute reticulocyte count < 60,000/microL (< 60 × 109/L)
Platelet count < 20,000/microL (< 20 × 109/L)
Treatment of Aplastic Anemia
Hematopoietic stem cell transplantation
If transplantation is not an option, immunosuppression with equine antithymocyte globulin and cyclosporine
In aplastic anemia, hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more can be curative and is the treatment of choice, particularly in younger patients with a matched donor. At diagnosis, siblings are evaluated for HLA (human leukocyte antigen) compatibility. Because transfusions pose a risk to subsequent transplantation, blood products are used only when essential.
In those patients unfit for transplant or lacking a donor, immunosuppressive treatment with equine antithymocyte globulin (ATG) combined with cyclosporine produces overall response rates of approximately 60 to 80%. Allergic reactions and serum sickness may occur. In refractory cases, thrombopoietin agonists have shown some efficacy in clinical trials, as have haploidentical bone marrow transplants ( 1 Treatment references Aplastic anemia is a disorder of the hematopoietic stem cell that results in a loss of blood cell precursors, hypoplasia or aplasia of bone marrow, and cytopenias in two or more cell lines ... read more , 2 Treatment references Aplastic anemia is a disorder of the hematopoietic stem cell that results in a loss of blood cell precursors, hypoplasia or aplasia of bone marrow, and cytopenias in two or more cell lines ... read more ).
Treatment references
1. DeZern AE, Zahurak M, Symons H, et al: Alternative donor transplantation with high-dose post-transplantation cyclophosphamide for refractory severe aplastic anemia. Biol Blood Marrow Transplant 23(3):498–504, 2017. doi: 10.1016/j.bbmt.2016.12.628
2. Winkler T, Fan X, Cooper J, et al: Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 133(24):2575–2585, 2019. doi: 10.1182/blood.2019000478
Key Points
Aplastic anemia involves panhypoplasia of the marrow with anemia, leukopenia, and thrombocytopenia.
Many cases are idiopathic, but chemicals, drugs, or radiation may be causes.
Bone marrow examination shows a variable degree of hypocellularity.
Treatment is with stem cell transplant or immunosuppression with equine antithymocyte globulin and cyclosporine.
